Viral infection prevents diabetes by inducing regulatory T cells through NKT cell-plasmacytoid dendritic cell interplay

Julien Diana, Vedran Brezar, Lucie Beaudoin, Marc Dalod, Andrew Mellor, Anna Tafuri, Matthias von Herrath, Christian Boitard, Roberto Mallone, Agnès Lehuen

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Type 1 diabetes (T1D) is an autoimmune disease resulting from T cell-mediated destruction of insulin-producing β cells, and viral infections can prevent the onset of disease. Invariant natural killer T cells (iNKT cells) exert a regulatory role in T1D by inhibiting autoimmune T cell responses. As iNKT cell-plasmacytoid dendritic cell (pDC) cooperation controls viral replication in the pancreatic islets, we investigated whether this cellular cross talk could interfere with T1D development during viral infection. Using both virus-induced and spontaneous mouse models of T1D, we show that upon viral infection, iNKT cells induce TGF-β-producing pDCs in the pancreatic lymph nodes (LNs). These tolerogenic pDCs convert naive anti-islet T cells into Foxp3+ CD4+ regulatory T cells (T reg cells) in pancreatic LNs. T reg cells are then recruited into the pancreatic islets where they produce TGF-β, which dampens the activity of viral- and islet-specific CD8+ T cells, thereby preventing T1D development in both T1D models. These findings reveal a crucial cooperation between iNKT cells, pDCs, and T reg cells for prevention of T1D by viral infection.

Original languageEnglish (US)
Pages (from-to)729-745
Number of pages17
JournalJournal of Experimental Medicine
Volume208
Issue number4
DOIs
Publication statusPublished - Apr 11 2011

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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